Usage Behaviour and Adoption Criteria for Mobile Health Solutions in Patients with Chronic Diseases in Gastroenterology.

Introduction: Mobile Health (mHealth) applications allow for new possibilities and opportunities in patient care. Their potential throughout the whole patient journey is undisputed. However, the eventual adoption by patients depends on their acceptance of and motivation to use mHealth applications as well as their adherence. Therefore, we investigated the motivation and drivers of acceptance for mHealth and developed an adapted model of the Unified Theory of Acceptance and Use of Technology (UTAUT2). Methods: We evaluated 215 patients with chronic gastroenterological diseases who answered a questionnaire including all model constructs with 7-point Likert scale items. Our model was adapted from the Unified Theory of Acceptance and Use in Technology 2 and includes influencing factors such as facilitating conditions, performance expectancy, hedonic motivation, social influence factors, effort expectancy, as well as personal empowerment and data protection concerns. Model evaluation was performed with structural equation modelling with PLS-SEM. Bootstrapping was performed for hypothesis testing. Results and Conclusion: Patients had a median age of 55.5 years, and the gender ratio was equally distributed. Forty percent received a degree from a university, college, technical academy, or engineering school. The majority of patients suffered from chronic liver disease, but patients with inflammatory bowel diseases, GI cancers, and pancreatic diseases were also included. Patients considered their general technology knowledge as medium to good or very good (78%). Actual usage of mHealth applications in general was rare, while the intention to use them was high. The leading acceptance factor for mHealth applications in our patient group was feasibility, both in terms of technical requirements and the intuitiveness and manageability of the application. Concerns about data privacy did not significantly impact the intention to use mobile devices. Neither the gamification aspect nor social influence factors played a significant role in the intention to use mHealth applications. Interpretation: Most of our patients were willing to spend time on a mHealth application specific to their disease on a regular basis. Acceptance and adherence are ensured by efficient utilization that requires minimum effort and compatible technologies as well as support in case of difficulties. Social influence and hedonic motivation, which were part of UTAUT2, as well as data security concerns, were not significantly influencing our patients' intention to use mHealth applications. A literature review revealed that drivers of acceptance vary considerably among different population and patient groups. Therefore, healthcare and mHealth providers should put effort into understanding their specific target groups' drivers of acceptance. We provided those for a cohort of patients from gastroenterology in this project.

Childhood Maltreatment and Amygdala Response to Interpersonal Threat in a Transdiagnostic Adult Sample: The Role of Trait Dissociation.

BACKGROUND: Childhood maltreatment (CM) confers risk for different mental disorders as well as transdiagnostic symptoms such as dissociation. Aberrant amygdala response to interpersonal threat may link CM to transdiagnostic psychopathology and has recently been shown to depend on type and developmental timing of CM experiences. Still, most studies on CM and threat-related amygdala response employ categorical disorder-specific perspectives and fail to consider type and timing of CM exposure. We aimed to investigate associations between CM, amygdala response to interpersonal threat, and dimensional psychopathological symptoms including trait dissociation in a transdiagnostic adult sample, specifically considering type, timing, and duration of CM. METHODS: We conducted a cross-sectional neuroimaging study in 141 participants with varying levels of CM, including mostly female participants with major depressive disorder (n = 36), posttraumatic stress disorder (n = 34), and somatic symptom disorder (n = 35) and healthy volunteers (n = 36). Participants underwent functional magnetic resonance imaging during an emotional face-matching task, completed the brief German interview version of the Maltreatment and Abuse Chronology of Exposure scale, and answered self-report measures of transdiagnostic CM-related symptoms including trait dissociation. Data were analyzed using a machine learning-based model comparison procedure. RESULTS: In our transdiagnostic sample, neither type nor timing or duration of CM predicted amygdala response to interpersonal threat. Instead, trait dissociation predicted blunted bilateral amygdala response and emerged as a possible mediator between CM and amygdala function. CONCLUSIONS: Trait dissociation may be an important confounder in the widely documented association between CM and threat-related amygdala response, which should be considered in future longitudinal studies.

The DNA methylation landscape of the human oxytocin receptor gene (OXTR): data-driven clusters and their relation to gene expression and childhood adversity.

The oxytocin receptor gene (OXTR) is of interest when investigating the effects of early adversity on DNA methylation. However, there is heterogeneity regarding the selection of the most promising CpG sites to target for analyses. The goal of this study was to determine functionally relevant clusters of CpG sites within the OXTR CpG island in 113 mother-infant dyads, with 58 of the mothers reporting childhood maltreatment (CM). OXTR DNA methylation was analyzed in peripheral/umbilical blood mononuclear cells. Different complexity reduction approaches were used to reduce the 188 CpG sites into clusters of co-methylated sites. Furthermore, associations between OXTR DNA methylation (cluster- and site-specific level) and OXTR gene expression and CM were investigated in mothers. Results showed that, first, CpG sections differed strongly regarding their statistical utility for research of individual differences in DNA methylation. Second, cluster analyses and Partial Least Squares (PLS) suggested two clusters consisting of intron1/exon2 and the protein-coding region of exon3, respectively, as most strongly associated with outcome measures. Third, cross-validated PLS regression explained 7% of variance in CM, with low cross-validated variance explained for the prediction of gene expression. Fourth, substantial mother-child correspondence was observed in correlation patterns within the identified clusters, but only modest correspondence outside these clusters. This study makes an important contribution to the mapping of the DNA methylation landscape of the OXTR CpG island by highlighting clusters of CpG sites that show desirable statistical properties and predictive value. We provide a Companion Web Application to facilitate the choice of CpG sites.

Structural Correlates of Lifetime Voice-Hearing in Patients with Borderline Personality Disorder: A Pilot Study.

INTRODUCTION: Auditory verbal hallucinations (AVH) are transdiagnostic phenomena that can occur in several mental disorders, including borderline personality disorder (BPD). Despite the transdiagnostic relevance of these symptoms, very little is known about neural signatures of AVH in BPD. METHODS: We used structural magnetic resonance imaging to investigate multiple markers of brain morphology in BPD patients presenting with a lifetime history of AVH (AVH, n = 6) versus BPD patients without AVH (nAVH, n = 10) and healthy controls (HC, n = 12). The Computational Anatomy Toolbox (CAT12) was used for surface-based morphometric analyses that considered cortical thickness (CTh), gyrification (CG), and complexity of cortical folding (CCF). Factorial models were used to explore differences between AVH patients and HC, as well as between the patient groups. RESULTS: Compared to HC, AVH patients showed distinct abnormalities in key regions of the language network, i.e., aberrant CTh and CG in right superior temporal gyrus and abnormal CCF in left inferior frontal gyrus. Further abnormalities were found in right prefrontal cortex (CTh) and left orbitofrontal cortex (CCF). Compared to nAVH patients, individuals with AVH showed abnormal CTh in right prefrontal cortex, along with CCF differences in right transverse temporal, superior parietal, and parahippocampal gyri. CG differences between the patient groups were found in left orbitofrontal cortex. CONCLUSION: The data suggest a transdiagnostic neural signature of voice-hearing that converges on key regions involved in speech generation and perception, memory and executive control. It is possible that cortical features of distinct evolutionary and genetic origin, i.e., CTh and CG/CCF, differently contribute to AVH vulnerability in BPD.

Neurostructural associations with traumatic experiences during child- and adulthood.

Adverse experiences can lead to severe mental health problems, such as posttraumatic stress disorder (PTSD), throughout the lifespan. In individuals with PTSD, both global and local brain volume reductions have been reported-especially in the amygdala and hippocampus-while the literature on childhood maltreatment suggests a strong dependency on the timing of adverse events. In the present study, we pooled data from two studies to contrast the effects of reported trauma exposure during neurodevelopmentally sensitive periods in early life with trauma exposure during adulthood. A total of 155 women were allocated into one of six age-matched groups according to the timing of traumatization (childhood vs adulthood) and psychopathology (PTSD vs trauma-exposed healthy vs trauma-naïve healthy). Volumes of the amygdala and hippocampus were compared between these groups. Six additional exploratory regions of interest (ROI) were included based on a recent meta-analysis. Amygdala volume was strongly dependent on the timing of traumatization: Smaller amygdala volumes were observed in participants with childhood trauma and PTSD compared to the healthy control groups. In contrast, larger amygdala volumes were observed in both groups with trauma exposure during adulthood compared to the trauma-naïve control group. Hippocampal volume comparisons revealed no statistically significant differences, although the descriptive pattern was similar to that found for the amygdala. The remaining exploratory ROIs showed significant group effects, but no timing effects. The timing might be an important moderator for adversity effects on amygdala volume, potentially reflecting neurodevelopmental factors. Albeit confounded by characteristics like trauma type and multiplicity, these findings pertain to typical childhood and adulthood trauma as often observed in clinical practice and speak against a simple association between traumatic stress and amygdala volume.

No evidence for intervention-associated DNA methylation changes in monocytes of patients with posttraumatic stress disorder.

DNA methylation patterns can be responsive to environmental influences. This observation has sparked interest in the potential for psychological interventions to influence epigenetic processes. Recent studies have observed correlations between DNA methylation changes and therapy outcome. However, most did not control for changes in cell composition. This study had two aims: first, we sought to replicate therapy-associated changes in DNA methylation of commonly assessed candidate genes in isolated monocytes from 60 female patients with post-traumatic stress disorder (PTSD). Our second, exploratory goal was to identify novel genomic regions with substantial pre-to-post intervention DNA methylation changes by performing whole-genome bisulfite sequencing (WGBS) in two patients with PTSD. Equivalence testing and Bayesian analyses provided evidence against physiologically meaningful intervention-associated DNA methylation changes in monocytes of PTSD patients in commonly investigated target genes (NR3C1, FKBP5, SLC6A4, OXTR). Furthermore, WGBS yielded only a limited set of candidate regions with suggestive evidence of differential DNA methylation pre- to post-therapy. These differential DNA methylation patterns did not prove replicable when investigated in the entire cohort. We conclude that there is no evidence for major, recurrent intervention-associated DNA methylation changes in the investigated genes in monocytes of patients with PTSD.

Open and reproducible science practices in psychoneuroendocrinology: Opportunities to foster scientific progress.

This perspective article was written by invitation of the editors in chief as a summary and extension of the symposium entitled Psychoneuroendocrine Research in the Era of the Replication Crisis which was held at the virtual meeting of the International Society of Psychoneuroendocrinology 2021. It highlights the opportunities presented by the application of open and reproducible scientific practices in psychoneuroendocrinology (PNE), an interdisciplinary field at the intersection of psychology, endocrinology, immunology, neurology, and psychiatry. It conveys an introduction to the topics preregistration, registered reports, quantifying the impact of equally-well justifiable analysis decisions, and open data and scripts, while emphasizing 'selfish' reasons to adopt such practices as individual researcher. Complementary to the call for adoption of open science practices, we highlight the need for methodological best practice guidelines in the field of PNE, which could further contribute to enhancing replicability of results. We propose concrete steps for future actions and provide links to additional resources for those interested in adopting open and reproducible science practices in future studies.

Survey on Open Science Practices in Functional Neuroimaging.

Replicability and reproducibility of scientific findings is paramount for sustainable progress in neuroscience. Preregistration of the hypotheses and methods of an empirical study before analysis, the sharing of primary research data, and compliance with data standards such as the Brain Imaging Data Structure (BIDS), are considered effective practices to secure progress and to substantiate quality of research. We investigated the current level of adoption of open science practices in neuroimaging and the difficulties that prevent researchers from using them. Email invitations to participate in the survey were sent to addresses received through a PubMed search of human functional magnetic resonance imaging studies that were published between 2010 and 2020. 283 persons completed the questionnaire. Although half of the participants were experienced with preregistration, the willingness to preregister studies in the future was modest. The majority of participants had experience with the sharing of primary neuroimaging data. Most of the participants were interested in implementing a standardized data structure such as BIDS in their labs. Based on demographic variables, we compared participants on seven subscales, which had been generated through factor analysis. Exploratory analyses found that experienced researchers at lower career level had higher fear of being transparent and researchers with residence in the EU had a higher need for data governance. Additionally, researchers at medical faculties as compared to other university faculties reported a more unsupportive supervisor with regards to open science practices and a higher need for data governance. The results suggest growing adoption of open science practices but also highlight a number of important impediments.

Advancing a temporal framework for understanding the biology of nonsuicidal self- injury: An expert review.

Nonsuicidal self-injury (NSSI) is a serious clinical problem, particularly for adolescents and young adults. NSSI is a complex behavior that emerges through the intersecting effects of social, psychological, and biological mechanisms. Although the social and psychological contributions to risk for developing NSSI are relatively well understood and have guided the development of effective psychosocial treatments for self-injury, the biological mechanisms underlying NSSI have just begun to come to light. To evaluate and categorize the biological research conducted on the topic of NSSI, we propose a model that distinguishes between trait and state markers. According to this model, risk factors and mechanisms involved in NSSI can be distinguished into both trait and state factors. We review the existing evidence on distal biological traits (predictors) of NSSI, proximal biological traits (correlates) of NSSI, and biological states directly preceding or following NSSI. We conclude by providing recommendations for future research on the neurobiology of NSSI.

Psychological structure and neuroendocrine patterns of daily stress appraisals.

Threat and challenge are two fundamental appraisal concepts of psychological stress theories, determined by the mismatch between demands and resources. Previous research has predominantly investigated the neuroendocrine correlates of stress appraisal in laboratory contexts during acute demanding situations. We tested whether the psychoneuroendocrinology of stress appraisals can also be investigated in naturalistic trans-contextual everyday life settings. Forty-two participants produced five daily saliva samples and provided concurrent questionnaire data on subjective stress, demands, resources, and the threat-challenge continuum over the course of five days (69% female; mean age = 22.8, range = 18-30 years). Momentary salivary cortisol and alpha amylase were predicted with three-level autoregressive linear mixed models. We found that both momentary cortisol and alpha amylase were elevated during higher subjective stress. In contrast, cortisol was not significantly related to a bipolar threat-challenge indicator. Moreover within-person response surface analyses showed no effect of the mismatch between demands and resources on either physiological stress indicator, but confirmed theoretically proposed effects on subjective threat-challenge, which was replicated in another intensive longitudinal (N = 61) and a large cross-sectional sample (N = 1194). In sum, our study (a) suggests robust relations between subjective stress and HPA/SAM axis activity on a moment-to-moment basis and (b) confirms theoretical predictions concerning stress appraisal and the mismatch between demands and resources on a psychological level. In contrast, no neuroendocrine patterns of threat-challenge were found, suggesting that neuroendocrine patterns might be context-specific and do not apply to a general demand-resource imbalance in everyday life.

Emotion dysregulation in borderline personality disorder: A fronto-limbic imbalance?

Borderline personality disorder is most consistently characterized as a disorder of the experience and regulation of emotions. Neuropathological models have predominantly explained these clinical traits with an imbalance between prefrontal regulatory and limbic emotion generating structures. Here, we review the current evidential state of the fronto-limbic imbalance hypothesis of borderline personality disorder, based on task-related functional magnetic resonance imaging research. In turn, we discuss challenges to the notion that (1) amygdala hyperreactivity underlies emotional hyperreactivity and deficits in (2) prefrontal activity or (3) fronto-limbic connectivity underly emotion regulation deficits. We offer several suggestions to improve consolidation and interpretation of research in this area.

Differential Effects of Early Adversity and Posttraumatic Stress Disorder on Amygdala Reactivity: The Role of Developmental Timing.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with altered processing of threat-related stimuli. Neurobiological models implicate right amygdala hyperreactivity in these alterations, but this potential biomarker also has been observed in individuals exposed to adverse childhood experiences (ACEs) (i.e., abuse and neglect) without psychopathology. Separation of the differential contributions of PTSD and ACEs to amygdala reactivity might benefit from incorporating the developmental timing of the events. METHODS: We conducted comprehensive retrospective interviews assessing ACEs for each life year between the ages of 1 and 17 years in a sample of 60 women exposed to trauma (including 34 participants with PTSD and 26 healthy participants). Functional magnetic resonance imaging was used to extract amygdala reactivity to threatening versus neutral scenes. Amygdala reactivity was predicted from PTSD diagnosis, total ACE severity, and ACE severity by life year using random forest regression. RESULTS: PTSD and ACEs significantly predicted reactivity in the right amygdala (R2 = 7%) but did not explain variance in the left amygdala. ACEs during both a prepubertal (ages 3 and 4) and a postpubertal (ages 16 and 17) period emerged as particularly predictive, while total ACE severity did not contribute to prediction. Follow-up analyses revealed a positive relationship between amygdala activity and PTSD and a negative relationship between amygdala activity and ACEs during predictive life years. CONCLUSIONS: The opposing effects of PTSD and ACEs caution against simplistic etiological and diagnostic interpretations of amygdala function. The identification of potentially sensitive periods for the effects of ACEs on amygdala reactivity to threat may help to uncover interactions between traumatization and development of PTSD.

Highs and lows: Genetic susceptibility to daily events.

Why people differ in their susceptibility to external events is essential to our understanding of personality, human development, and mental disorders. Genes explain a substantial portion of these differences. Specifically, genes influencing the serotonin system are hypothesized to be differential susceptibility factors, determining a person's reactivity to both positive and negative environments. We tested whether genetic variation in the serotonin transporter (5-HTTLPR) is a differential susceptibility factor for daily events. Participants (N = 326, 77% female, mean age = 25, range = 17-36) completed smartphone questionnaires four times a day over four to five days, measuring stressors, uplifts, positive and negative affect. Affect was predicted from environment valence in the previous hour on a within-person level using three-level autoregressive linear mixed models. The 5-HTTLPR fulfilled all criteria of a differential susceptibility factor: Positive affect in carriers of the short allele (S) was less reactive to both uplifts and stressors, compared to homozygous carriers of the long allele (L/L). This pattern might reflect relative affective inflexibility in S-allele carriers. Our study provides insight into the serotonin system's general role in susceptibility and highlights the need to assess the whole spectrum of naturalistic experiences.

Oxytocin and the stress buffering effect of social company: a genetic study in daily life.

Social relationships are a crucial determinant of both mental and physical health. This effect is partly due to social buffering of stress. Animal studies suggest that social buffering is mediated via the oxytocin system, while studies in humans are sparse and limited by the low ecological validity of laboratory settings. In the present study, participants (N = 326) completed smartphone questionnaires four times a day over 4 to 5 days, measuring stressors, negative affect, and social context to assess social buffering. We found that under stress, participants reported a higher need for social company. Further, the impact of prior stressful events on momentary negative affect was attenuated by the perceived pleasantness of current social company. This social buffering effect was moderated by haplotypes of the oxytocin receptor gene, based on two well-described single nucleotide polymorphisms (rs2268498, rs53576). Effects were robust when controlling for gender and age, applying different data quality criteria, and even apparent in genotype-based analyses. Our findings demonstrate that social buffering and its modulation by oxytocin system characteristics have implications for life as lived outside the laboratory.